New Device Lets Scientists Scan Mice Brains While Awake And Moving

Animal and pathology researchers received exciting news this week from a team of scientists representing the US Department of Energy´s (DOE) Thomas Jefferson National Accelerator Facility, Oak Ridge National Laboratory, Johns Hopkins Medical School and the University of Maryland. The collaborative team announced that they have developed a method for imaging the brains of mice while they are awake and unrestrained.

Typically, the dynamic imaging of mice is used to track changes in brain chemistry caused by the progression of disease or the use of a drug. This method is an effective research tool for developing better ways to diagnose disease along with formulating better and more effective treatments.

Until this new method was introduced, animal researchers had to either restrain or drug their mouse subjects in order to study their brains. The problem with this method is that the results are often affected by the anesthesia and physical restraints. This was especially problematic for scientists who focused their research on Alzheimer´s disease, dementia and Parkinson´s disease.

The new method, which the team calls AwakeSPECT, allows researchers to acquire functional images of the brains of conscious, unbound and un-anesthetized mice. Their first use of this new system aimed at documenting the effects of anesthesia on the action of a dopamine transporter imaging compound. These compounds have been used in previous studies of the diseases just mentioned.

The ℠SPECT´ in AwakeSPECT stands for Single-Photon Emission Computed Tomography. The new system allows researchers to observe a radionuclide that collects in specific areas of the brain where it emits gamma rays. These rays are documented by a detector over the course of several scans taken from numerous angles. Once collected, the scans are combined in an algorithm that produces a three-dimensional image.

“The AwakeSPECT system does regular SPECT imaging of mice. SPECT is a nuclear medicine imaging technique that’s used in humans for various types of diagnostic studies. It’s also used in animal studies to facilitate the development and understanding of disease physiology,” says Jefferson Lab’s Drew Weisenberger, who led the multi-institutional collaboration and directed the development of the SPECT system.

The new system requires Jefferson Lab custom-built cameras for the radionuclide imaging as well as a system that is able to process the collected data into the 3D images. The Oak Ridge National Laboratory developed the infrared camera that tracks the mouse´s movement. The final component is a commercially available CT system that is used to provide the researchers with additional anatomical information.

For anyone who has ever had to undergo a CT scan, one of the most trying parts of the procedure is the requirement to remain absolutely motionless. According to the team, the beauty of this new system is that the animal subject — and potentially humans at some point in the future — will be able to move, if even in a somewhat limited fashion. The DOE´s Jefferson Lab has already been awarded two patents for the newly developed technologies that made the creation of this system possible.

“We developed this system that, while acquiring SPECT images, uses infrared cameras that track the location and pose of the head. We use that information to then computationally remove motion artifacts from our SPECT imaging,” said Weisenberger.

The research team published their study results online in The Journal of Nuclear Medicine. They were also able to show that the use of anesthetic could negatively impact drug uptake studies.

“We’ve shown the technology works. Now, you just have to make it a tool that more people will readily use” Weisenberger added.

According to Weisenberger, this is just the beginning for their new AwakeSPECT imager. The team plans to next update the infrared tracking system, employing newer technology to improve the SPECT imager and working to make the overall system more intuitive so animal researchers will find it easier to operate.

Initial funding for the AwakeSPECT system was provided by the DOEs Office of Science. The National Institutes of Health provided additional support.